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Gauthier M et al . Variability of perfusion parameters using DCE-US commonly recognized as a functional imaging technique able to evaluate such therapies as it is a sensitive and highly available modality allowing early prediction of tumor response to treatments based on changes in vascularity before any morphological ones occur. Research frontiers Microbubble contrast agents for DCE-US have developed during the past 10 years and are currently approved in Europe, Asia and Canada. Nowadays, ultrasound provides an ideal imaging modality for angiogenesis: it is widely available, not ionizing, low cost and provides real time imaging. However, until now, information on intra-operator variability in perfusion parameter measurements performed using DCE-US is lacking. In this study, the authors evaluated such variability and highlighted values similar to previous findings using other imaging modalities. Innovations and breakthroughs DCE-US is supported by the French National Cancer Institute which is currently studying the technique in several pathologies to establish the optimal perfusion parameters and timing for quantitative anticancer efficacy assessments: currently 400 patients with 1096 DCE-US demonstrated that the area under the curve quantified at 1 mo could be a robust parameter to predict response at 6 mo. The following study is the first one analyzing intra-operator variability in perfusion parameter measurements performed using DCE-US. Our study would suggest that DCE-US technique has comparable intra-operator variability than other functional imaging modalities that are currently used in routine. Applications By evaluating intra-operator variability in perfusion parameter measurements performed using DCE-US, this study may confirm the interest of dynamic contrast enhanced-ultrasonography as functional imaging in anti-angiogenic therapy evaluations. Terminology DCE-US involves the use of microbubble contrast agents and specialized imaging techniques to evaluate blood flow and tissue perfusion. Intra-operator variability studies aim to determine the variation in measurements performed by a single operator and instrument on the same item and under the same conditions. Peer review This is an interesting study and may draw the readers’ attention because the authors evaluated the feasibility and reproducibility of DCE-US through in vitro and in vivo. Moreover, I think that this study would guide the readers about the methods of basic research in the areas of radiology. Unfortunately, strength of reported findings is limited by some experimental constraints and manuscript presentation needs several improvements before publication. REFERENCES 1 Lanza GM, Caruthers SD, Winter PM, Hughes MS, Schmieder AH, Hu G, Wickline SA. Angiogenesis imaging with vascular-constrained particles: the why and how. Eur J Nucl Med Mol Imaging 2010; 37 Suppl 1: S114-S126 2 Eisenbrey JR, Forsberg F. Contrast-enhanced ultrasound for molecular imaging of angiogenesis. Eur J Nucl Med Mol Imaging 2010; 37 Suppl 1: S138-S146 3 Kalva SP, Namasivayam S, Vasuedo Sahani D. Imaging Angiogenesis. In: Teicher BA, Ellis LM, editors. Cancer Drug Discovery and Development: Antiangiogenic Agents in Cancer Therapy. Totowa, NJ: Humana Press, 2008: 189-203 4 Lassau N, Chami L, Péronneau P. Imagerie de contraste ultrasonore pour l’évaluation précoce des thérapeutiques ciblées. In: Tranquart F, Correas JM, Bouakaz A, editors. Echographie de contraste. Paris: Springer, 2007: 81-86 5 Therasse P, Arbuck SG, Eisenhauer EA, Wanders J, Kaplan RS, Rubinstein L, Verweij J, Van Glabbeke M, van Oosterom AT, Christian MC, Gwyther SG. New guidelines to evaluate the response to treatment in solid tumors. 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Radiological Society of North America. 95th Scientific Assembly and Annual Meeting; 2009 No 29-Dec 4; Mc Cormick Place, Chicago 24 Veltmann C, Lohmaier S, Schlosser T, Shai S, Ehlgen A, Pohl C, Becher H, Tiemann K. On the design of a capillary flow phantom for the evaluation of ultrasound contrast agents at very low flow velocities. Ultrasound Med Biol 2002; 28: 625-634 25 Meyer-Wiethe K, Cangür H, Seidel GU. Comparison of different mathematical models to analyze diminution kinetics of ultrasound contrast enhancement in a flow phantom. Ultrasound Med Biol 2005; 31: 93-98 80 March 28, 2011|Volume 3|Issue 3|
26 Lavisse S, Lejeune P, Rouffiac V, Elie N, Bribes E, Demers B, Vrignaud P, Bissery MC, Brulé A, Koscielny S, Péronneau P, Lassau N. Early quantitative evaluation of a tumor vasculature disruptive agent AVE8062 using dynamic contrastenhanced ultrasonography. Invest Radiol 2008; 43: 100-111 27 Verbeek XA, Willigers JM, Prinzen FW, Peschar M, Ledoux LA, Hoeks AP. High-resolution functional imaging with ultrasound contrast agents based on RF processing in an in vivo kidney experiment. Ultrasound Med Biol 2001; 27: 223-233 28 Correas JM, Burns PN, Lai X, Qi X. Infusion versus bolus of an ultrasound contrast agent: in vivo dose-response measurements of BR1. Invest Radiol 2000; 35: 72-79 29 Gorce JM, Arditi M, Schneider M. Influence of bubble size distribution on the echogenicity of ultrasound contrast agents: a study of SonoVue. Invest Radiol 2000; 35: 661-671 30 Vicenzini E, Delfini R, Magri F, Puccinelli F, Altieri M, Santoro A, Giannoni MF, Bozzao L, Di Piero V, Lenzi GL. 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Growth and dissolution of an encapsulated contrast microbubble: effects of encapsulation permeability. Ultrasound Med Biol 2009; 35: 1385-1396 41 Kwan JJ, Borden MA. Microbubble dissolution in a multigas environment. Langmuir 2010; 26: 6542-6548 42 Casciaro S, Errico RP, Conversano F, Demitri C, Distante A. Experimental investigations of nonlinearities and destruction mechanisms of an experimental phospholipid-based ultrasound contrast agent. Invest Radiol 2007; 42: 95-104 43 Ng CS, Raunig DL, Jackson EF, Ashton EA, Kelcz F, Kim KB, Kurzrock R, McShane TM. Reproducibility of perfusion parameters in dynamic contrast-enhanced MRI of lung and liver tumors: effect on estimates of patient sample size in clinical trials and on individual patient responses. AJR Am J Roentgenol 2010; 194: W134-W140 44 Marcus CD, Ladam-Marcus V, Cucu C, Bouché O, Lucas L, WJR|www.wjgnet.com Gauthier M et al . Variability of perfusion parameters using DCE-US Hoeffel C. Imaging techniques to evaluate the response to treatment in oncology: current standards and perspectives. Crit Rev Oncol Hematol 2009; 72: 217-238 45 Evelhoch JL, LoRusso PM, He Z, DelProposto Z, Polin L, Corbett TH, Langmuir P, Wheeler C, Stone A, Leadbetter J, Ryan AJ, Blakey DC, Waterton JC. Magnetic resonance imaging measurements of the response of murine and human tumors to the vascular-targeting agent ZD6126. Clin Cancer Res 2004; 10: 3650-3657 46 Morgan B, Utting JF, Higginson A, Thomas AL, Steward WP, Horsfield MA. A simple, reproducible method for monitoring the treatment of tumours using dynamic contrast-enhanced MR imaging. Br J Cancer 2006; 94: 1420-1427 47 Wells P, Jones T, Price P. Assessment of inter- and intrapatient variability in C15O2 positron emission tomography measurements of blood flow in patients with intra-abdominal cancers. Clin Cancer Res 2003; 9: 6350-6356 48 Cenic A, Nabavi DG, Craen RA, Gelb AW, Lee TY. Dynamic CT measurement of cerebral blood flow: a validation study. AJNR Am J Neuroradiol 1999; 20: 63-73 49 Groves AM, Goh V, Rajasekharan S, Kayani I, Endozo R, Dickson JC, Menezes LJ, Shastry M, Habib SB, Ell PJ, Hutton BF. CT coronary angiography: quantitative assessment of myocardial perfusion using test bolus data-initial experience. Eur Radiol 2008; 18: 2155-2163 50 Miller JC, Pien HH, Sahani D, Sorensen AG, Thrall JH. Imaging angiogenesis: applications and potential for drug development. J Natl Cancer Inst 2005; 97: 172-187 51 Thomas AL, Morgan B, Horsfield MA, Higginson A, Kay A, Lee L, Masson E, Puccio-Pick M, Laurent D, Steward WP. Phase I study of the safety, tolerability, pharmacokinetics, and pharmacodynamics of PTK787/ZK 222584 administered twice daily in patients with advanced cancer. J Clin Oncol 2005; 23: 4162-4171 52 Willett CG, Boucher Y, di Tomaso E, Duda DG, Munn LL, Tong RT, Chung DC, Sahani DV, Kalva SP, Kozin SV, Mino M, Cohen KS, Scadden DT, Hartford AC, Fischman AJ, Clark JW, Ryan DP, Zhu AX, Blaszkowsky LS, Chen HX, Shellito PC, Lauwers GY, Jain RK. Direct evidence that the VEGFspecific antibody bevacizumab has antivascular effects in human rectal cancer. Nat Med 2004; 10: 145-147 53 Meijerink MR, van Cruijsen H, Hoekman K, Kater M, van Schaik C, van Waesberghe JH, Giaccone G, Manoliu RA. The use of perfusion CT for the evaluation of therapy combining AZD2171 with gefitinib in cancer patients. Eur Radiol 2007; 17: 1700-1713 54 Lassau N, Lamuraglia M, Vanel D, Le Cesne A, Chami L, Jaziri S, Terrier P, Roche A, Leclere J, Bonvalot S. Doppler US with perfusion software and contrast medium injection in the early evaluation of isolated limb perfusion of limb sarcomas: prospective study of 49 cases. Ann Oncol 2005; 16: 1054-1060 55 Miles KA, Griffiths MR. Perfusion CT: a worthwhile enhancement? Br J Radiol 2003; 76: 220-231 56 Lassau N, Chebil M, Koscielny S, Chami L, Bendjilali R, Roche A. Dynamic Contrast-enhanced Ultrasonography (DCE-US) with Quantification for the Early Evaluation of HCC Treated by Bevacizumab: Which Parameters? Radiological Society of North America. 95th Scientific Assembly and Annual Meeting; 2009 Nov 29-Dec 4; Chicago: Mc Cormick Place 57 Lassau N, Chebil M, Chami L, Bidault S, Girard E, Roche A. Dynamic contrast-enhanced ultrasonography (DCE-US): a new tool for the early evaluation of antiangiogenic treatment. Target Oncol 2010; 5: 53-58 58 Quaia E, D'Onofrio M, Palumbo A, Rossi S, Bruni S, Cova M. Comparison of contrast-enhanced ultrasonography versus baseline ultrasound and contrast-enhanced computed tomography in metastatic disease of the liver: diagnostic performance and confidence. Eur Radiol 2006; 16: 1599-1609 S- Editor Cheng JX L- Editor O’Neill M E- Editor Zheng XM 81 March 28, 2011|Volume 3|Issue 3|
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